L-Homolysine dihydrochloride

Sulfated peptides are plant hormones that are active at nanomolar concentrations. The sulfation at one or more tyrosine residues is catalysed by tyrosylprotein sulfotransferase (TPST), which is encoded by a single-copy gene. The sulfate group is provided by the co-substrate 3'-phosphoadenosine 5'-phosphosulfate (PAPS), which links synthesis of sulfated signaling peptides to sulfur metabolism. The precursor proteins share a conserved DY-motif that is implicated in specifying tyrosine sulfation. Several sulfated peptides undergo additional modification such as hydroxylation of proline and glycosylation of hydroxyproline. The modifications render the secreted signaling molecules active and stable. Several sulfated signaling peptides have been shown to be perceived by leucine-rich repeat receptor-like kinases (LRR-RLKs) but have signaling pathways that, for the most part, are yet to be elucidated. Sulfated peptide hormones regulate growth and a wide variety of developmental processes, and intricately modulate immunity to pathogens. While basic research on sulfated peptides has made steady progress, their potential in agricultural and pharmaceutical applications has yet to be explored.

Sulfation pathways have recently come into the focus of biomedical research. For steroid hormones and related compounds, sulfation represents an additional layer of regulation as sulfated steroids are more water-soluble and tend to be biologically less active. For steroid diols, an additional sulfation is possible, carried out by the same sulfotransferases that catalyze the first sulfation step. The steroid disulfates that are formed are the focus of this review. We discuss both their biochemical production as well as their putative biological function. Steroid disulfates have also been linked to various clinical conditions in numerous untargeted metabolomics studies. New analytical techniques exploring the biosynthetic routes of steroid disulfates have led to novel insights, changing our understanding of sulfation in human biology. They promise a bright future for research into sulfation pathways, hopefully too for the diagnosis and treatment of several associated diseases.

Chemical protein synthesis has achieved tremendous progress in the past decades. With the development of chemical ligation as powerful tools, the scope of synthetic protein is greatly expanded. Proteoglycans are a class of sulfated glycoproteins widely distributed on the cell surface and in the extracellular matrix, which are extensively engaged in cellular communication events. Consisting of protein backbone and glycosaminoglycan(s) side chain, proteoglycans are highly complex and heterogeneous in nature. Chemical synthesis provides facile and reliable approach to these molecules, with defined glycan structure and sulfation pattern. One remaining problem is that the acid-labile sulfates could hardly survive during the typical solid phase peptide synthesis (SPPS) process. In this chapter, strategic design of a "glycopeptide cassette" for the preparation of sulfated glycoprotein is described. In particular, we provide protocols for the chemical synthesis of ectodomain fragment (23-120) of sulfated glycoprotein syndecan-1.